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A Chiral Pentafluorinated Isopropyl Group via Iodine(I)/(III) Catalysis
Author(s) -
Meyer Stephanie,
Häfliger Joel,
Schäfer Michael,
Molloy John J.,
Daniliuc Constantin G.,
Gilmour Ryan
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202015946
Subject(s) - geminal , chemistry , vicinal , isopropyl , catalysis , stereochemistry , isostere , group (periodic table) , medicinal chemistry , organic chemistry
An I(I)/(III) catalysis strategy to construct an enantioenriched fluorinated isostere of the i Pr group is reported. The difluorination of readily accessible α‐CF 3 ‐styrenes is enabled by the in situ generation of a chiral ArIF 2 species to forge a stereocentre with the substituents F, CH 2 F and CF 3 (up to 95 %, >20:1 vicinal:geminal difluorination). The replacement of the metabolically labile benzylic proton results in a highly preorganised scaffold as was determined by X‐ray crystallography (π→σ* and stereoelectronic gauche σ→σ* interactions). A process of catalyst editing is disclosed in which preliminary validation of enantioselectivity is placed on a structural foundation.